Biomaterials
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Thermoresponsive polymers (TRPs) have been extensively investigated as smart devices, drug delivery systems and protein conjugates due to their unique phase transition properties. Here, we report the unusual influence of TRPs in blood clotting and the mechanism by which TRPs change the three dimensional organization of blood clot structure. Ten different TRPs with lower critical solution temperatures ranged from 26 to 80 °C are studied. ⋯ The plasma phase of the blood coagulation is not affected in presence of TRPs. We anticipate that our results will have significant implications on the use of TRPs in applications where blood contact is essential. These observations may also open up new avenues, for example, in the design of new generation antithrombotics.
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The function of type II collagen in cartilage is well documented and its importance for long bone development has been implicated. However, the involvement of type II collagen in bone marrow derived mesenchymal stem cell (BMSC) osteogenesis has not been well investigated. This study elucidated the pivotal role of type II collagen in BMSC osteogenesis and its potential application to bone healing. ⋯ In a segmental defect model in rats, type II collagen-HA/TCP-implanted rats showed significant callus formation at the reunion site, and a higher SFI (sciatic function index) scoring as comparing to other groups were also observed at 7, 14, and 21 day post-surgery. Collectively, type II collagen serves as a better modulator during early osteogenic differentiation of BMSCs by facilitating RUNX2 activation through integrin α2β1-FAK-JNK signaling axis, and enhance bone defect repair through an endochondral ossification-like process. These results advance our understanding about the cartilaginous ECM-BMSC interaction, and provide perspective for bone defect repair strategies.
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Previous reports in the literature investigating chondrogenesis in mesenchymal progenitor cell (MPC) cultures have confirmed the chondro-inductive potential of pentosan polysulphate (PPS), a highly sulphated semi-synthetic polysaccharide, when added as a soluble component to culture media under standard aggregate-assay conditions or to poly(ethylene glycol)/hyaluronic acid (PEG/HA)-based hydrogels, even in the absence of inductive factors (e.g. TGFβ). In this present study, we aimed to assess whether a 'bound' PPS would have greater activity and availability over a soluble PPS, as a media additive or when incorporated into PEG/HA-based hydrogels. ⋯ When encapsulated in the hydrogels, MPCs retained good viability and rapidly adopted a rounded morphology. Histological analysis of both GAG and collagen deposition after 21 days showed that the incorporation of the bound-PPS into the hydrogel resulted in increased matrix formation when compared to the addition of soluble PPS to the hydrogel, or the hydrogel alone. We believe that this new generation injectable, degradable hydrogel, incorporating now a covalently bound-PPS, when combined with MPCs, has the potential to assist cartilage regeneration in a multitude of therapeutic targets, including for intervertebral disc (IVD) degeneration.
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Injectable calcium phosphate cement (ICPC) has been applied to enhance the tendon-to-bone healing. However, its slow degradation delays the osteointegration of grafted tendon in bone tunnels. We therefore constructed a synthetic biomaterial of ICPC combined with recombined bone xenograft granules (RBX). ⋯ In addition, little remnants were observed in ICPCB-3 group. Moreover, the maximum loads to failure of ICPCB-3 group was significantly higher than ICPC group at 24 weeks (P < 0.01). We conclude that the ICPCB composite, with a porous structure and better osteointegration effect, has direct clinical instruction to arthroscopic techniques of the ACL reconstruction.
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The objective of this study was to investigate the ability of mesenchymal stem cells (MSC) genetically engineered with stromal cell-derived factor-1 (SDF-1) to heal skin wounds. When transfected with SDF-1 plasmid DNA, MSC which were isolated from the bone marrow of rats, secreted SDF-1 for 7 days. In vitro cell migration assay revealed that the SDF-1-engineered MSC (SDF-MSC) enhanced the migration of MSC and dermal fibroblasts to a significantly greater extent than MSC. ⋯ The length of the neoepithelium and the number of blood vessels newly formed were significantly larger. A cell-tracing experiment with fluorescently labeled cells demonstrated that the percent survival of SDF-MSC in the tissue treated was significantly high compared with that of MSC. It was concluded that SDF-1 genetic engineering is a promising way to promote the wound healing activity of MSC for a skin defect.